Classic Hodgkin lymphoma and Castleman disease: an entity appears to be emerging

Hodgkin lymphoma is a B cell neoplasm characterized by Hodgkin and Reed-Sternberg (HRS) cells in an inflammatory background. Classic Hodgkin lymphoma (CHL) accounts for approximately 90% of all cases of HL and four types are recognized in the World Health Organization (WHO) classification: lymphocyte-rich, nodular sclerosis, mixed cellularity, and lymphocyte depleted. Castleman disease (CD) is a designation used for a heterogeneous group of diseases that involve lymph nodes. Histologically, there are hyaline vascular and plasma cell variants, the latter including human herpes virus 8 (HHV8)-positive and HHV8-negative subsets. In this study, we describe three men, 45-57 years of age, one HIV-positive, who had coexistent CHL and CD. All patients had the interfollicular variant of CHL and HHV8-negative plasma cell variant CD. Immunohistochemical analysis supported the diagnosis of CHL; the HRS cells were positive for CD15, CD30, and PAX-5 (dim). In two cases, the HRS cells and the plasma cells of CD expressed interleukin-6 (IL-6). Our review of the literature identified 34 cases of coexistent CHL and CD reported previously. In aggregate, about two-thirds of all cases of CHL have been the interfollicular variant and around 90% of CD cases were plasma cell variant, HHV8-negative in the subset of cases tested. We suggest that interfollicular variant CHL and plasma cell variant CD may be a distinct entity with a common pathogenesis, possibly related to IL-6 dysregulation. The few cases in the literature describing other forms of CHL and hyaline vascular variant CD are different from the entity reported here, with a different pathogenesis, likely similar to focal Castleman-like changes that have been described in association with various types of non-Hodgkin lymphoma.